Peripheral immune response and axonal degeneration in the hind paw skin of mice with experimental autoimmune encephalomyelitis
Bibliographic record
Abstract
• EAE leads to significant changes in the innervation density of hind paw skin. • Responses are sex specific and difference in reinnervation emerged by four weeks post-immunization. • Increased inflammation is also observed in the hind paw skin at disease onset that coincided with tactile hypersensitivity. Multiple sclerosis (MS) is traditionally considered a central nervous system (CNS) disease characterized by chronic inflammation and demyelination in the brain and spinal cord, often resulting in debilitating neuropathic pain. While the primary mechanisms of pain in MS are attributed to central mechanisms, recent evidence suggests that peripheral nervous system (PNS) changes may also contribute. Peripheral neurons in the dorsal root ganglia (DRG), which relay sensory information to the CNS, can undergo inflammation-induced structural and functional changes that amplify pain sensitivity. In human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), inflammation and neuronal injury have been observed in the DRG, yet the role of the PNS in MS pain remains underexplored. To investigate peripheral contributions to pain in EAE, we examined disease-induced changes in hind paw cutaneous tissue and found increased inflammation at disease onset that coincided with tactile hypersensitivity. Intraepidermal nerve fiber (IENF) loss was observed in both sexes at disease onset; however, a sex-specific difference in reinnervation emerged by four weeks post-immunization, with females exhibiting significant reinnervation while males did not. These findings identify sex-dependent patterns of peripheral innervation during EAE and raise the possibility that peripheral mechanisms may contribute differently across sexes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".